Precision Medicine Identifies Those At-Risk of Rapid Kidney Decline

Researchers using precision medicine discovered signs of rapid decline in kidney function from patients with type 1 diabetes. Diabetes is the leading cause of kidney failure in the United States. However, scientists have struggled to determine when patients with type 1 or type 2 diabetes are at risk for progressive kidney disease.

In the past, the assessment of kidney function required looking at estimated glomerular filtration rate and urine albumin excretion. However, both tests lack predictive abilities in early-stage diabetes when kidney function is normal.

The therapeutic approach to type 1 and type 2 diabetic kidney disease also has followed a similar method despite having different biological causes.

As more advanced technology becomes available, a multi-institution international research team set out to understand what lipid biomarkers could predict the progression of diabetic kidney disease and how do the predictors differentiate between type 1 and type 2 diabetes.

The case-control study used more than 800 patients with type 1 diabetes. Data from patients with type 2 diabetes had already been collected in a previous study by Farsad Afshinnia, MD, a nephrologist at the University of Michigan Health.

The case group comprised individuals with rapidly declining rates of kidney function compared to the control subjects who showed preserved kidney function over a four-year follow-up period.

Afshinnia and his team spotted differences in lipid predictors of diabetic disease between type 1 and type 2 patients. These biomarkers were identifiable in early-stage diabetes when glomerular filtration and urine albumin excretion are normal.

“These findings not only provide a platform for risk stratification, but also suggest the underlying mechanism of progressive kidney disease,” Afshinnia said in a press release. “Understanding the mechanism may be a future target for therapeutic intervention.”

In previous studies of patients with type 2 diabetes, Afshinnia and senior author Subramaniam Pennathur, MD, also the chief of nephrology at the University of Michigan Health and director of the Michigan O’Brien Kidney Translational Center, have seen certain lipids impact the progression of diabetic kidney disease in patients.

However, by using a method of chronic disease management, lipid alternation can be medicated by insulin resistance in those with type 2 diabetes. Since those with type 1 diabetes and normal kidney function are typically sensitive to insulin, researchers suspected that the biomarkers for kidney disease progress would differ between type 1 and type 2 diabetes.

The research team hypothesized they would see a unique pattern of circulated free fatty acids, acylcarnitines, and glycerolipids between type 1 and type 2 diabetes, indicating which biomarkers can cause a rapid or slow decline of kidney function.

“Both types of diabetes can result in diabetic kidney disease, later requiring dialysis or transplantation,” Pennathur added. “The current standard of care for patients with diabetes is to optimize their blood sugar and blood pressure control, but better biochemical markers of kidney function decline in patients with normal kidney function is lacking.”

By using this form of precision medicine, providers could accurately identify patients at high risk for loss of kidney function.

After studying more than 300 lipids from the more than 800 participants with type 1 diabetes, researchers discovered 47 lipids that differed between rapid and slow kidney function decliners. Additionally, plasma concentrations of three different circulating free fatty acids (FFA 20:2, 24:3, and 18:2) appeared more frequently in rapid decliners than slow.

The team also found that patients with type 1 diabetes with the potential for rapid decline of kidney function revealed a higher plasma abundance of unsaturated free fatty acids and a lower plasma abundance of saturated free fatty acids.

According to the team, a critical finding was the possible role of phospholipase A1 and A2 being the underlying system for affecting the fatty acids in rapid decliners.

“This panel of lipids is unique only for type 1 diabetic kidney disease,” said Pennathur. “That suggests a unique type 1 diabetic kidney disease specific risk-marker panel. We may be able to manipulate phospholipase A1 and A2 in future studies to see if it’s a potential target for preventing the progression of diabetic kidney disease at its early stages.”

“What we’ve discovered suggests there’s a panel of lipids that can predict a rapid decline of kidney function at such an early stage of type 1 diabetic kidney disease when both the glomerular filtration rate and the urine albumin-creatinine ratio are normal,” Afshinnia noted.

The research could be a potential breakthrough in the treatment of diabetic kidney disease. By enforcing preventive care strategies, kidney function can be preserved rather than fighting an advanced disease when damage has become irreversible.